Regulation of beta‐adrenergic receptor expression in rat liver

To begin defining the factors regulating neurotransmitter receptor expression, we examined beta‐adrenergic receptors in rat liver in vivo and in primary liver cultures under defined hormonal conditions. β‐receptors described a remarkable developmental profile in vivo, increasing fivefold between embryonic days 16 and 20, and decreasing tenfold by early adulthood. The developmental decrease reflected reduced receptor number without a change in receptor properties. The ontogenetic decrease appeared to be specific for β‐receptors α‐receptors developed in a hyperbolic fashion, reaching high plateau values by the third postnatal week. Adult rat liver cells plated into culture re‐expressed high β‐receptor levels, exhibiting a 4‐8‐fold increase. A similar pattern of expression of the β‐receptors, having similar pharmacological properties, was observed in primary liver cultures maintained in serum‐free medium, in a serum‐supplemented medium or in several variations of a serum‐free, hormonally defined medium designed for primary liver cultures. Thus, the degree of expression of the β‐receptors was not found affected by various hormones, by serum, or by any medium condition. By contrast, the degree of expression of the β‐receptors was markedly sensitive to cell density. High expression of the β‐receptors was observed at low cell densities (1‐3 × 10 6 cells/150 mm dish), and low expression or no expression was observed in confluent cultures (10‐20 × 10 6 cells/150 mm dish). Our experiments suggest that β‐receptor expression does not follow an immutable program, but may be regulated by density‐dependent cell‐cell interactions.